Schistosomiasis causes liver fibrosis, anemia, impairs child growth and development, and affects 200 million people globally. While many people still lack access to basic treatment, schistosomiasis persists in some areas where aggressive disease control measures have been implemented for reasons we do not fully understand. In southwest China, for example, schistosomiasis has reemerged and persists despite multi-year disease control programs including treatment, health education, sanitation improvements and snail control. We aim to harness recent advances in genomics and leverage a prior longitudinal study of schistosomiasis reemergence in order to address two questions we view as essential to understanding the persistence of schistosomiasis: 1) do individuals with consecutive infections have persistent, uncured infections or incident infections and 2) are incident infections the progeny of local parasite populations observed previously? To answer these questions, we will optimize a recently developed high-throughput reduced representation method, restriction-site- associated DNA sequencing (RADSeq), to assess Schistosoma japonicum genomic diversity at high- resolution. Parasites will be obtained from an archive of S. japonicum miracidia collected from 2007 to 2010 and prospective infection surveys conducted as part of this project, allowing analysis of helminth diversity and relatedness over a seven year period. S. japonicum miracidia will be analyzed using existing microsatellite genotyping methods and RADSeq. The parallel analysis using both microsatellites and RADSeq will allow us to compare statistical power and efficiency of coarse-vs. high-resolution measures of genomic diversity and evaluate optimal sampling strategies for future projects. Our research synthesizes expertise at the forefront of genomics and schistosomiasis control, with the broad goal of advancing efforts to interrupt the transmission of schistosomiasis and other human helminthiases.